Standard microelectrode techniques will be used to study the electrophysiology and pharmacology of spontaneous impulse initiation in partially depolarized canine cardiac Purkinje fibers and myocardium. Abnormal automaticity will be induced in Purkinje fibers with BaCl2 or will be studied in infarct zone Purkinje fibers at 24 hours after coronary ligation. Triggered activity from afterdepolarizations will be studied in isolated Purkinje fibers treated with N-acetyl procainamide (early afterdepolarizations) or infarct zone Purkinje fibers (delayed afterdepolarizations). The responses of all these types of abnormal impulses will be studied by standard stimulation protocols (e.g., overdrive, premature stimulation, intracellular current pulses), and will be compared with the results of analogous studies on automaticity in normal fibers. We will study the effects of standard and experimental antiarrhythmic drugs on these experimental models of abnormal impulse initiation; in particular, we will study the effects of local anesthetic agents (lidocaine, procainamide, and their derivatives), propranolol, ethmozin, and slow inward current blocking agents (nifedipine, verapamil Mn2 ion, AHR-2666) on abnormal automaticity and triggered activity. These studies should give us insights into the electrophysiological mechanisms of cardiac arrhythmias, and may lead to improved pharmacotherapy. If time permits, we will extend a recently developed unipolar recording method to detect extracellular potentials from the endocardial surface of the in situ canine ventricle, to attempt to detect early afterdepolarizations and triggered activity in arrhythmic hearts.